Identification of early predictive biomarkers for severe cytokine release syndrome in pediatric patients with chimeric antigen receptor T-cell therapy

CAR-T cell therapy is a revolutionary new treatment for hematological malignancies, but it can also result in significant adverse effects, with cytokine release syndrome (CRS) being the most common and potentially life-threatening. The identification of biomarkers to predict the severity of CRS is crucial to ensure the safety and efficacy of CAR-T therapy. To achieve this goal, we characterized the expression profiles of seven cytokines, four conventional biochemical markers, and five hematological markers prior to and following CAR-T cell infusion. Our results revealed that IL-2, IFN-γ, IL-6, and IL-10 are the key cytokines for predicting severe CRS (sCRS). Notably, IL-2 levels rise at an earlier stage of sCRS and have the potential to serve as the most effective cytokine for promptly detecting the condition's onset. Furthermore, combining these cytokine biomarkers with hematological factors such as lymphocyte counts can further enhance their predictive performance. Finally, a predictive tree model including lymphocyte counts, IL-2, and IL-6 achieved an accuracy of 85.11% (95% CI = 0.763-0.916) for early prediction of sCRS. The model was validated in an independent cohort and achieved an accuracy of 74.47% (95% CI = 0.597-0.861). This new prediction model has the potential to become an effective tool for assessing the risk of CRS in clinical practice.